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We discuss the problems in attracting girls into physics. We present some of the projects undertaken in various countries to ameliorate the problem, and we conclude with some follow‐up suggestions that can be implemented in all countries.
DOI: 10.1063/1.1505270Research Article| October 01, 2002 Pronounced central uplift identified in the Bosumtwi impact structure, Ghana, using multichannel seismic reflection data Christopher A. Scholz; Christopher A. Scholz 1204 Heroy Geology Laboratory, Department of Earth Sciences, Syracuse University, Syracuse, New York 13244, USA Search for other works by this author on: GSW Google Scholar Tobias Karp; Tobias Karp 2Institut für Geowissenschaften, Abteilung Geophysik Otto-Hahn-Platz 1, 24118 Kiel, Germany Search for other works by this author on: GSW Google Scholar Keely M. Brooks; Keely M. Brooks 3204 Heroy Geology Laboratory, Department of Earth Sciences, Syracuse University, Syracuse, New York 13244, USA Search for other works by this author on: GSW Google Scholar Bernd Milkereit; Bernd Milkereit 4Department of Physics, University of Toronto, 60 St. George Street, Toronto, Ontario M5S 1A7, Canada Search for other works by this author on: GSW Google Scholar Philip Y.O. Amoako; Philip Y.O. Amoako 5Ghana Geological Survey, P.O. Box M80, Accra, Ghana Search for other works by this author on: GSW Google Scholar Justice A. Arko Justice A. Arko 6Institute of Mining and Mineral Engineering, University of Science and Technology, Kumasi, Ghana Search for other works by this author on: GSW Google Scholar Author and Article Information Christopher A. Scholz 1204 Heroy Geology Laboratory, Department of Earth Sciences, Syracuse University, Syracuse, New York 13244, USA Tobias Karp 2Institut für Geowissenschaften, Abteilung Geophysik Otto-Hahn-Platz 1, 24118 Kiel, Germany Keely M. Brooks 3204 Heroy Geology Laboratory, Department of Earth Sciences, Syracuse University, Syracuse, New York 13244, USA Bernd Milkereit 4Department of Physics, University of Toronto, 60 St. George Street, Toronto, Ontario M5S 1A7, Canada Philip Y.O. Amoako 5Ghana Geological Survey, P.O. Box M80, Accra, Ghana Justice A. Arko 6Institute of Mining and Mineral Engineering, University of Science and Technology, Kumasi, Ghana Publisher: Geological Society of America Received: 22 Jan 2002 Revision Received: 13 Jun 2002 Accepted: 18 Jun 2002 First Online: 02 Jun 2017 Online ISSN: 1943-2682 Print ISSN: 0091-7613 Geological Society of America Geology (2002) 30 (10): 939–942. https://doi.org/10.1130/0091-7613(2002)030<0939:PCUIIT>2.0.CO;2 Article history Received: 22 Jan 2002 Revision Received: 13 Jun 2002 Accepted: 18 Jun 2002 First Online: 02 Jun 2017 Cite View This Citation Add to Citation Manager Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Search Site Citation Christopher A. Scholz, Tobias Karp, Keely M. Brooks, Bernd Milkereit, Philip Y.O. Amoako, Justice A. Arko; Pronounced central uplift identified in the Bosumtwi impact structure, Ghana, using multichannel seismic reflection data. Geology 2002;; 30 (10): 939–942. doi: https://doi.org/10.1130/0091-7613(2002)030<0939:PCUIIT>2.0.CO;2 Download citation file: Ris (Zotero) Refmanager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentBy SocietyGeology Search Advanced Search Abstract The Lake Bosumtwi impact structure is the youngest and best-preserved complex terrestrial impact crater and serves as an important reference site for the study of cratering processes. Because the impacting body struck continental crystalline target rocks and not a submerged sedimentary platform, no significant backwash processes have modified the crater morphology. Not only may Bosumtwi contain the best-preserved central uplift structure on Earth, but it is the most accessible relatively large, young crater in the solar system generated in a large gravity field. There is a well-established link between the Lake Bosumtwi impact structure and the Ivory Coast tektite field, and the lacustrine sediments within the crater contain a unique 1 m.y. record of paleoclimate in the continental tropics south of the Sahel. Eight profiles of marine-type multichannel seismic reflection (MCS) data were acquired from the 8-km-diameter, ∼75-m-deep lake that fills much of the crater. These were augmented by wide-angle seismic data acquired with ocean-bottom hydrophones. MCS data reveal a well-defined central uplift near the northwest-central part of the lake and a maximum postimpact lacustrine sediment thickness of ∼310 m. The central uplift structure has a diameter of 1.9 km and a maximum height of 130 m above the annular moat inside the crater. An intermediate velocity layer (3200 m/s) beneath the lacustrine sediment is interpreted as fallback breccia or a breccia-melt horizon. The measured apparent depth of the crater (da) is 500 m, implying a slightly higher aspect ratio for the structure than predicted from published empirical relationships. The Bosumtwi structure is a small complex crater that deviates slightly from trends predicted from classical scaling laws, perhaps because of the effects of a large gravity field. You do not have access to this content, please speak to your institutional administrator if you feel you should have access.
DOI: 10.1130/0091-7613(2002)030<0939:pcuiit>2.0.co;2Cereals (maize, sorghum, millet, rice) are extremely important crops grown in Africa for human consumption. Of the various insect pests attacking cereal crops in Africa, lepidopteran stem borers are by far the most injurious. All 21 economically important stem borers of cultivated grasses in Africa are indigenous except Chilo partellus, which invaded the continent from India, and C. sacchariphagus, which has recently been found in sugarcane in Mozambique. C. partellus is competitively displacing indigenous stem borers in East and southern Africa. A parasitoid, Cotesia flavipes, was introduced from Pakistan for biological control of C. partellus and caused a 32-55% decrease in stem borer densities. This article is an attempt to summarize the status of knowledge about economically important cereal stem borers in Africa with emphasis on their distribution, pest status and yield losses, diapause, natural enemies, cultural control, host plant resistance, and biological control. Special attention is given to Busseola fusca and C. partellus, the most important pests of maize and grain sorghum.
DOI: 10.1146/annurev.ento.47.091201.145254In the last two decades, growing interest in the production and utilisation of safou (Dacryodes edulis), an indigenous fruit tree species of West and Central Africa, has stimulated work on the selection of genetic resources with desired traits, timing of fruit collection and the tree's reproductive biology. In this context, 58 germplasm accessions were collected in Nigeria during 1998. The periodicity of fruiting was found to vary geographically and a preliminary characterisation showed a wide range of variation in fruit traits. About 4% of fruits were seedless. The importance of this knowledge is discussed with regard to genetic selection and improvement, and the need to extend germplasm collection activities to wild relatives of the species. In the humid forest zone, the main insect pollinator is Meliponula erythra. Allogamy has been found to be the main reproduction system of D. edulis, while hermaphrodite flowers are self-compatible.
DOI: 10.1080/14728028.2002.9752411Physics of Semiconductor Devices covers both basic classic topics such as energy band theory and the gradual-channel model of the MOSFET as well as advanced concepts and devices such as MOSFET short-c
DOI: 10.1007/b117561As a discipline, phylogenetics is becoming transformed by a flood of molecular data. These data allow broad questions to be asked about the history of life, but also present difficult statistical and computational problems. Bayesian inference of phylogeny brings a new perspective to a number of outstanding issues in evolutionary biology, including the analysis of large phylogenetic trees and complex evolutionary models and the detection of the footprint of natural selection in DNA sequences.
DOI: 10.1126/science.1065889Plasmids belonging to Escherichia coli incompatibility group Q are relatively small (approximately 5 to 15 kb) and able to replicate in a remarkably broad range of bacterial hosts. These include gram-positive bacteria such as Brevibacterium and Mycobacterium and gram-negative bacteria such as Agrobacterium, Desulfovibrio, and cyanobacteria. These plasmids are mobilized by several self-transmissible plasmids into an even more diverse range of organisms including yeasts, plants, and animal cells. IncQ plasmids are thus highly promiscuous. Recently, several IncQ-like plasmids have been isolated from bacteria found in environments as diverse as piggery manure and highly acidic commercial mineral biooxidation plants. These IncQ-like plasmids belong to different incompatibility groups but have similar broad-host-range replicons and mobilization properties to the IncQ plasmids. This review covers the ecology, classification, and evolution of IncQ and IncQ-like plasmids.
DOI: 10.1128/mmbr.65.4.481-496.2001Prostaglandins and leukotrienes are potent eicosanoid lipid mediators derived from phospholipase-released arachidonic acid that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and actions are blocked by clinically relevant nonsteroidal anti-inflammatory drugs, the newer generation coxibs (selective inhibitors of cyclooxygenase-2), and leukotriene modifiers. The prime mode of prostaglandin and leukotriene action is through specific G protein-coupled receptors, many of which have been cloned recently, thus enabling specific receptor agonist and antagonist development. Important insights into the mechanisms of inflammatory responses, pain, and fever have been gleaned from our current understanding of eicosanoid biology.
DOI: 10.1126/science.294.5548.1871One of the most remarkable aspects of an animal's behavior is the ability to modify that behavior by learning, an ability that reaches its highest form in human beings. For me, learning and memory have proven to be endlessly fascinating mental processes because they address one of the fundamental features of human activity: our ability to acquire new ideas from experience and to retain these ideas over time in memory. Moreover, unlike other mental processes such as thought, language, and consciousness, learning seemed from the outset to be readily accessible to cellular and molecular analysis. I, therefore, have been curious to know: What changes in the brain when we learn? And, once something is learned, how is that information retained in the brain? I have tried to address these questions through a reductionist approach that would allow me to investigate elementary forms of learning and memory at a cellular molecular level-as specific molecular activities within identified nerve cells.
DOI: 10.1126/science.1067020▪ Abstract Contributions from the field of population biology hold promise for understanding and managing invasiveness; invasive species also offer excellent opportunities to study basic processes in population biology. Life history studies and demographic models may be valuable for examining the introduction of invasive species and identifying life history stages where management will be most effective. Evolutionary processes may be key features in determining whether invasive species establish and spread. Studies of genetic diversity and evolutionary changes should be useful for understanding the potential for colonization and establishment, geographic patterns of invasion and range expansion, lag times, and the potential for evolutionary responses to novel environments, including management practices. The consequences of biological invasions permit study of basic evolutionary processes, as invaders often evolve rapidly in response to novel abiotic and biotic conditions, and native species evolve in response to the invasion.
DOI: 10.1146/annurev.ecolsys.32.081501.114037Preface to the Second Edition. Preface to the First Edition. Acknowledgments for the Second Edition. Acknowledgments for the First Edition. 1. Introduction and Preview. 1.1 Preview of the Book. 2. Entropy, Relative Entropy, and Mutual Information. 2.1 Entropy. 2.2 Joint Entropy and Conditional Entropy. 2.3 Relative Entropy and Mutual Information. 2.4 Relationship Between Entropy and Mutual Information. 2.5 Chain Rules for Entropy, Relative Entropy, and Mutual Information. 2.6 Jensen's Inequality and Its Consequences. 2.7 Log Sum Inequality and Its Applications. 2.8 Data-Processing Inequality. 2.9 Sufficient Statistics. 2.10 Fano's Inequality. Summary. Problems. Historical Notes. 3. Asymptotic Equipartition Property. 3.1 Asymptotic Equipartition Property Theorem. 3.2 Consequences of the AEP: Data Compression. 3.3 High-Probability Sets and the Typical Set. Summary. Problems. Historical Notes. 4. Entropy Rates of a Stochastic Process. 4.1 Markov Chains. 4.2 Entropy Rate. 4.3 Example: Entropy Rate of a Random Walk on a Weighted Graph. 4.4 Second Law of Thermodynamics. 4.5 Functions of Markov Chains. Summary. Problems. Historical Notes. 5. Data Compression. 5.1 Examples of Codes. 5.2 Kraft Inequality. 5.3 Optimal Codes. 5.4 Bounds on the Optimal Code Length. 5.5 Kraft Inequality for Uniquely Decodable Codes. 5.6 Huffman Codes. 5.7 Some Comments on Huffman Codes. 5.8 Optimality of Huffman Codes. 5.9 Shannon-Fano-Elias Coding. 5.10 Competitive Optimality of the Shannon Code. 5.11 Generation of Discrete Distributions from Fair Coins. Summary. Problems. Historical Notes. 6. Gambling and Data Compression. 6.1 The Horse Race. 6.2 Gambling and Side Information. 6.3 Dependent Horse Races and Entropy Rate. 6.4 The Entropy of English. 6.5 Data Compression and Gambling. 6.6 Gambling Estimate of the Entropy of English. Summary. Problems. Historical Notes. 7. Channel Capacity. 7.1 Examples of Channel Capacity. 7.2 Symmetric Channels. 7.3 Properties of Channel Capacity. 7.4 Preview of the Channel Coding Theorem. 7.5 Definitions. 7.6 Jointly Typical Sequences. 7.7 Channel Coding Theorem. 7.8 Zero-Error Codes. 7.9 Fano's Inequality and the Converse to the Coding Theorem. 7.10 Equality in the Converse to the Channel Coding Theorem. 7.11 Hamming Codes. 7.12 Feedback Capacity. 7.13 Source-Channel Separation Theorem. Summary. Problems. Historical Notes. 8. Differential Entropy. 8.1 Definitions. 8.2 AEP for Continuous Random Variables. 8.3 Relation of Differential Entropy to Discrete Entropy. 8.4 Joint and Conditional Differential Entropy. 8.5 Relative Entropy and Mutual Information. 8.6 Properties of Differential Entropy, Relative Entropy, and Mutual Information. Summary. Problems. Historical Notes. 9. Gaussian Channel. 9.1 Gaussian Channel: Definitions. 9.2 Converse to the Coding Theorem for Gaussian Channels. 9.3 Bandlimited Channels. 9.4 Parallel Gaussian Channels. 9.5 Channels with Colored Gaussian Noise. 9.6 Gaussian Channels with Feedback. Summary. Problems. Historical Notes. 10. Rate Distortion Theory. 10.1 Quantization. 10.2 Definitions. 10.3 Calculation of the Rate Distortion Function. 10.4 Converse to the Rate Distortion Theorem. 10.5 Achievability of the Rate Distortion Function. 10.6 Strongly Typical Sequences and Rate Distortion. 10.7 Characterization of the Rate Distortion Function. 10.8 Computation of Channel Capacity and the Rate Distortion Function. Summary. Problems. Historical Notes. 11. Information Theory and Statistics. 11.1 Method of Types. 11.2 Law of Large Numbers. 11.3 Universal Source Coding. 11.4 Large Deviation Theory. 11.5 Examples of Sanov's Theorem. 11.6 Conditional Limit Theorem. 11.7 Hypothesis Testing. 11.8 Chernoff-Stein Lemma. 11.9 Chernoff Information. 11.10 Fisher Information and the Cram-er-Rao Inequality. Summary. Problems. Historical Notes. 12. Maximum Entropy. 12.1 Maximum Entropy Distributions. 12.2 Examples. 12.3 Anomalous Maximum Entropy Problem. 12.4 Spectrum Estimation. 12.5 Entropy Rates of a Gaussian Process. 12.6 Burg's Maximum Entropy Theorem. Summary. Problems. Historical Notes. 13. Universal Source Coding. 13.1 Universal Codes and Channel Capacity. 13.2 Universal Coding for Binary Sequences. 13.3 Arithmetic Coding. 13.4 Lempel-Ziv Coding. 13.5 Optimality of Lempel-Ziv Algorithms. Compression. Summary. Problems. Historical Notes. 14. Kolmogorov Complexity. 14.1 Models of Computation. 14.2 Kolmogorov Complexity: Definitions and Examples. 14.3 Kolmogorov Complexity and Entropy. 14.4 Kolmogorov Complexity of Integers. 14.5 Algorithmically Random and Incompressible Sequences. 14.6 Universal Probability. 14.7 Kolmogorov complexity. 14.9 Universal Gambling. 14.10 Occam's Razor. 14.11 Kolmogorov Complexity and Universal Probability. 14.12 Kolmogorov Sufficient Statistic. 14.13 Minimum Description Length Principle. Summary. Problems. Historical Notes. 15. Network Information Theory. 15.1 Gaussian Multiple-User Channels. 15.2 Jointly Typical Sequences. 15.3 Multiple-Access Channel. 15.4 Encoding of Correlated Sources. 15.5 Duality Between Slepian-Wolf Encoding and Multiple-Access Channels. 15.6 Broadcast Channel. 15.7 Relay Channel. 15.8 Source Coding with Side Information. 15.9 Rate Distortion with Side Information. 15.10 General Multiterminal Networks. Summary. Problems. Historical Notes. 16. Information Theory and Portfolio Theory. 16.1 The Stock Market: Some Definitions. 16.2 Kuhn-Tucker Characterization of the Log-Optimal Portfolio. 16.3 Asymptotic Optimality of the Log-Optimal Portfolio. 16.4 Side Information and the Growth Rate. 16.5 Investment in Stationary Markets. 16.6 Competitive Optimality of the Log-Optimal Portfolio. 16.7 Universal Portfolios. 16.8 Shannon-McMillan-Breiman Theorem (General AEP). Summary. Problems. Historical Notes. 17. Inequalities in Information Theory. 17.1 Basic Inequalities of Information Theory. 17.2 Differential Entropy. 17.3 Bounds on Entropy and Relative Entropy. 17.4 Inequalities for Types. 17.5 Combinatorial Bounds on Entropy. 17.6 Entropy Rates of Subsets. 17.7 Entropy and Fisher Information. 17.8 Entropy Power Inequality and Brunn-Minkowski Inequality. 17.9 Inequalities for Determinants. 17.10 Inequalities for Ratios of Determinants. Summary. Problems. Historical Notes. Bibliography. List of Symbols. Index.
DOI: 10.1002/0471200611Function estimation/approximation is viewed from the perspective of numerical optimization in function space, rather than parameter space. A connection is made between stagewise additive expansions and steepest-descent minimization. A general gradient descent “boosting” paradigm is developed for additive expansions based on any fitting criterion.Specific algorithms are presented for least-squares, least absolute deviation, and Huber-M loss functions for regression, and multiclass logistic likelihood for classification. Special enhancements are derived for the particular case where the individual additive components are regression trees, and tools for interpreting such “TreeBoost” models are presented. Gradient boosting of regression trees produces competitive, highly robust, interpretable procedures for both regression and classification, especially appropriate for mining less than clean data. Connections between this approach and the boosting methods of Freund and Shapire and Friedman, Hastie and Tibshirani are discussed.
DOI: 10.1214/aos/1013203451The fundamental physical properties of doped ${\mathrm{LaMnO}}_{3},$ generically termed ``manganites,'' and much of the underlying physics, were known more than 40 years ago. This article first reviews progress made at that time, the concept of double exchange in particular, and points out the missing elements that have led to a massive resurgence of interest in these and related materials. More recent research is then described, treating first the ground states that emerge as divalent atoms are substituted for trivalent La. A wide range of ground states appear, including ferromagnetic metals, orbital- and charge-ordered antiferromagnets, and more complex stripe and spin-glass states. Because of the interest in so-called colossal magnetoresistance that occurs in the ferromagnetic/metallic composition range, a section is devoted to reviewing the atypical properties of that phase. Next the high-temperature phase is examined, in particular, evidence for the formation of self-trapped small polarons and the importance of Jahn-Teller coupling in this process. The transitions between the high-temperature polaronic phase and the ferromagnetic and charge-ordered states are treated in a fourth section. In each section, the authors stress the competition among charge, spin, and lattice coupling and review the current state of theoretical understanding. They conclude with some comments on the impact that research on these materials has on our understanding of doped oxides and other strongly correlated electronic materials.
DOI: 10.1103/revmodphys.73.583Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in basrelief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (> or = 50 microns), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.
DOI: 10.1146/annurev.bioeng.3.1.335We present Conditional Random Fields, a framework \nfor building probabilistic models to segment \nand label sequence data. Conditional random \nfields offer several advantages over hidden \nMarkov models and stochastic grammars \nfor such tasks, including the ability to relax \nstrong independence assumptions made in those \nmodels. Conditional random fields also avoid \na fundamental limitation of maximum entropy \nMarkov models (MEMMs) and other discriminative \nMarkov models based on directed graphical \nmodels, which can be biased towards states \nwith few successor states. We present iterative \nparameter estimation algorithms for conditional \nrandom fields and compare the performance of \nthe resulting models to HMMs and MEMMs on \nsynthetic and natural-language data.
Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.
DOI: 10.1128/mmbr.65.2.232-260.2001Schematic of the major branch pathways of flavonoid biosynthesis, starting with general phenylpropanoid metabolism and leading to the nine major subgroups: the colorless chalcones, aurones, isoflavonoids, flavones, flavonols, and flavandiols (gray boxes), and the anthocyanins, condensed tannins, and phlobaphene pigments (colored boxes). The first committed step is catalyzed by chalcone synthase (CHS), which uses malonyl CoA and 4-coumaroyl CoA as substrates. Only a few examples are shown of the enormous variety of end products that arise through terminal modification by the addition of sugars as well as methyl, ferulate, and other groups. P450 hydoxylases that may function as membrane anchors for multienzyme assemblies are indicated in red. The photographs illustrate the three major classes of pigments in the model plants, snapdragon, Arabidopsis, maize, and petunia. Root nodulation by rhizobia, which involves flavone as well as flavanone and isoflavone signal molecules, is also shown, in this case for sweet clover (Melilotus alba). Enzyme names are abbreviated as follows: cinnamate-4-hydroxylase (C4H), chalcone isomerase (CHI), chalcone reductase (CHR), chalcone synthase (CHS), 4-coumaroyl:CoA-ligase (4CL), dihydroflavonol 4-reductase (DFR), 7,2′-dihydroxy, 4′-methoxyisoflavanol dehydratase (DMID), flavanone 3-hydroxylase (F3H), flavone synthase (FSI and FSII), flavonoid 3′ hydroxylase (F3′H) or flavonoid 3′5′ hydroxylase (F3′5′H), isoflavoneO-methyltransferase (IOMT), isoflavone reductase (IFR), isoflavone 2′-hydroxylase (I2′H), isoflavone synthase (IFS), leucoanthocyanidin dioxygenase (LDOX), leucoanthocyanidin reductase (LCR), O-methyltransferase (OMT), Phe ammonia-lyase (PAL), rhamnosyl transferase (RT), stilbene synthase (STS), UDPG-flavonoid glucosyl transferase (UFGT), and vestitone reductase (VR). Photographs are courtesy of Cathie Martin (John Innes Centre, Norwich, UK; Antirrhinum), Francesca Quattrocchio (Free University, Amsterdam; petunia), Erich Grotewold (Ohio State University, Columbus; maize), and Yimei Lin and Ann Hirsch (University of California, Los Angeles; sweet clover). A well-known physiological function of the anthocyanin pigments and flavonol copigments is the recruitment of pollinators and seed dispersers. These compounds also have figured into some of the major scientific breakthroughs of the past 150 years, including Mendel's elucidation of genetics, seed coat color being one of the major characters followed in his experiments with peas (Pisum sativum), and McClintock's discovery of transposable elements, which moved in and out of flavonoid biosynthetic genes expressed in maize kernels. Anthocyanins more recently have aided in understanding the phenomenon of cosuppression, particularly in petunia (Petunia hybrida). But besides providing beautiful pigmentation in flowers, fruits, seeds, and leaves, flavonoids also have key roles in signaling between plants and microbes, in male fertility of some species, in defense as antimicrobial agents and feeding deterrents, and in UV protection. The “early” steps in the pathway are found even in the bryophytes (mosses) and it has been suggested that synthesis of flavones, flavanones, and flavonols may have evolved first to provide chemical messengers and then UV sunscreens (Stafford, 1991). Flavonoids also have significant activities when ingested by animals, and there is great interest in their potential health benefits, particularly for compounds such as isoflavonoids, which have been linked to the anticancer benefits of soy-based foods, and the stilbenes in red wine that are believed to contribute to reduced heart disease. In recent years, much effort has been directed at elucidating the flavonoid biosynthetic pathway from a molecular genetic point of view. Mutants affecting flavonoid synthesis have been isolated in a variety of plant species based on alterations in flower and seed pigmentation. Maize, snapdragon (Antirrhinum majus), and petunia were established as the first major experimental models in this system, and work in these species led to the isolation of many flavonoid structural and regulatory genes (for review, see Holton and Cornish, 1995; Mol et al., 1998). Arabidopsis more recently has helped facilitate analysis of the regulation and subcellular organization of the flavonoid pathway. One unique aspect of using Arabidopsis for studying flavonoid biosynthesis is that all but one of the enzymes of central flavonoid metabolism (leading to flavonols and anthocyanins) are encoded by single-copy genes. The exception is flavonol synthase (FLS), which appears to be encoded by six genes, two of which may not be expressed (A. Bandara, D. Owens, and B. Winkel-Shirley, unpublished data). Genetic loci for both structural (TableI) and regulatory genes are scattered across the Arabidopsis genome and have been identified largely on the basis of mutations that abolish or reduce pigmentation in the seed coat. As a result, the loci were named transparent testa by Maarten Koornneef (Wageningen Agricultural University, The Netherlands), who isolated many of the first mutants in this class in the 1980s (for review, see Koornneef, 1990). The initial collection of 12 tt mutants has been expanded to include 21 members (tt1–19 plus ttg1 and ttg2), largely through directed searches in the Koornneef lab for new lines producing yellow or pale-brown seeds, and indirectly, by Loic Lepiniec and coworkers at the Institut National de la Recherche Agronomique (Versailles, France), in screens for plants exhibiting reduced seed dormancy. Transposon and activator tagging have been used to isolate additional mutations in genes either directly or indirectly involved in flavonoid biosynthesis (Wisman et al., 1998; Kubo et al., 1999; Borevitz et al., 2000). As a result most of the structural genes, as well as a number of regulatory genes, have now been correlated with specific mutant loci in Arabidopsis. Although Arabidopsis does not appear to use flavonoids in all of the same ways as some other species (for example, in defense or for male fertility), the Arabidopsis mutants are helping to define a role for these compounds in essential processes such as UV protection (Li et al., 1993; Landry et al., 1995) and the regulation of auxin transport (Murphy et al., 2000; Brown et al., 2001). Genetic loci for cloned flavonoid enzymes in Arabidopsis1-a Similar information for maize, petunia, and snapdragon is described by Holton and Cornish (1995). Based on the AGI map, 11/12/00; numbers in parentheses refer to P1 or bacterial artificial chromosome clones on which these sequences reside. Transposon-tagged mutant for FLS1 (Wisman et al., 1998). A. Tanaka (personal communication). Genetic loci for cloned flavonoid enzymes in Arabidopsis1-a Similar information for maize, petunia, and snapdragon is described by Holton and Cornish (1995). Based on the AGI map, 11/12/00; numbers in parentheses refer to P1 or bacterial artificial chromosome clones on which these sequences reside. Transposon-tagged mutant for FLS1 (Wisman et al., 1998). A. Tanaka (personal communication). Several important new genes required for flavonoid biosynthesis have been characterized in a variety of plant species over the past few years, including some with direct practical applications. One of these is the Arabidopsis BANYULS gene, which encodes a DFR-like protein that may be an LCR that catalyzes an early step in condensed tannin biosynthesis (Fig. 1; Devic et al., 1999). A locus identified independently as anthocyanin spotted testa (ast;Tanaka et al., 1997), with a very similar mutant phenotype, now appears to be identical to BAN (A. Tanaka, personal communication). Controlling condensed tannin levels in forage crops has long been of interest, both to improve nutritional value either by increasing or decreasing endogenous levels and to provide amounts sufficient to control pasture bloat. Some success has been achieved by modulating late steps in the central flavonoid pathway, such as the DFR reaction, for which cloned genes were previously available (Morris and Robbins, 1997). The LCR gene may provide an opportunity to direct metabolic engineering efforts more specifically to the proanthocyanidin branch pathway. Several breakthroughs have been made in the isoflavonoid pathway, including the isolation of the first IFS genes. Biochemical and genetic data have long suggested that this enzyme is a member of the cytochrome P450 oxygenase family of enzymes. This was confirmed by Shin-ichi Ayabe's laboratory (Nihon University, Fujisawa, Kanagawa, Japan) with the isolation of IFS from a licorice (Glycyrrhiza echinata) cell line that produces isoflavonoids upon elicitation (Akashi et al., 1999). At the same time, Richard Dixon's group (The Noble Foundation, Ardmore, OK) identified an IFS gene from soybean (Glycine max) by functional screening of candidate P450 cDNAs in insect cells (Steele et al., 1999), whereas a group at DuPont Wilmington, DE identified the same gene as well as a second IFS using a similar screen in yeast (Saccharamyces cerevisiae; Jung et al., 2000). Both isoforms of soybean IFS appear to be able to use both liquiritigenin and naringenin as substrates to produce genistein or daidzein, respectively (Fig. 1), although naringenin is used less efficiently. The DuPont group showed that soybean IFS1 can function to convert naringenin to genistein in transgenic Arabidopsis and, more recently, in tobacco (Nicotiana tabacum) and maize (Yu et al., 2000). They have also shown that introduction of IFS1 together with chalcone reductase, which provides the additional substrate, liquiritigenin, results in the synthesis of daidzein in maize. Nancy Paiva's laboratory (The Noble Foundation) is attempting to express VR in tobacco plants; this enzyme is one of several that will be required to engineer production of the isoflavonoid, medicarpin, the major phytoalexin produced by alfalfa (Medicago sativa) in response to fungal pathogens (Fig. 1;Watson and Paiva, 2000). A cDNA encoding the cytochrome P450 protein, I2′H, another enzyme required for medicarpin biosynthesis (Fig. 1), has also been isolated from licorice (Akashi et al., 1998). Together, these advances are laying the foundation for engineering isoflavonoid biosynthesis for agronomic and nutritional enhancement of a wide variety of crop plants that do not normally synthesize these compounds. There may also be more immediately feasible applications in the engineering of legumes, for example, to improve the palatability of soy milk by down-regulating isoflavonoid synthesis in soybean seeds. Efforts to engineer flower color have also led to some interesting developments in the last few years. The hydroxylation pattern of the B ring of anthocyanins is a major determinant of the color of these pigments. All flavonoids carry a hydroxyl group at the 4′ position, including the pink-to-red cyanidin-based pigments. Hydroxylation at two variable positions is controlled by the P450 enzymes, F3′H, which leads to brick-red to orange pelargonidin-based pigments, and F3′5′H, which is required for synthesis of purple and blue delphinidin-based pigments (Fig. 1). Several years ago, workers at Florigene isolated two F3′5′H genes from petunia based on sequence homology to other p450s, a pattern of high-level expression in flowers, and correlation with theHf1 and Hf2 loci (Holton et al., 1993). Cloning of the first F3′H gene took a bit longer, but a petunia gene was eventually isolated using a similar approach (Brugliera et al., 1999). Together with Chris Cobbett (The University of Melbourne, Parkville, Victoria, Australia), this group also identified the F3′H gene in Arabidopsis by chromosome walking to the tt7 locus (C. Cobbett, personal communication); the same gene has been identified independently based on information from the Arabidopsis Genome Project (Schoenbohm et al., 2000; Saslowsky and Winkel-Shirley, 2001). It is unfortunate that these genes are not, by themselves, sufficient for engineering altered flower color in horticulturally important species, for example, by overexpression in roses (Rosa spp.) and carnations (Dianthus caryophyllus) that normally lack F3′5′H activity and therefore do not produce blue or purple pigments (Brugliera et al., 2000). However, it has been shown that a specific cytochrome b5 is required for maximal activity of the petunia F3′5′H as an to the P450 reductase that is with cytochrome P450 et al., 1999). It is that the group at Florigene recently that when the petunia F3′5′H and b5 genes are together into flower color is from red to a purple (Brugliera et al., 2000). It appears that the long blue may be at are also being made in understanding the regulation of flavonoid biosynthesis, particularly as a result of molecular genetic such as tagging and This has led to the of a number of regulatory that are to in the between that the pathway and well-known flavonoid such as the and and of maize. In has been made in genes that expression of pathway enzymes, which are specific to proanthocyanidin and anthocyanin include a new class of flavonoid regulatory by in petunia et al., and in Arabidopsis et al., 1999), that and are to the of appears to be a protein that expression of the recently cloned protein, et al., 1999). from in several including role not in flavonoid synthesis but in cell and the production of seed A gene, has recently been isolated from maize personal which may some on the and function of this new class of regulatory In a of phenylpropanoid has been cloned in Arabidopsis, when results in purple et al., 2000). In addition to providing into regulation of phenylpropanoid the lines may provide a new into Arabidopsis genes that function the branch to condensed tannins, a of genes based on the The Arabidopsis which has a similar to has identified another class of flavonoid regulatory a member of the family that two and 1998). the regulatory pathways flavonoid synthesis and involves at two This of has been in one other species, a of Arabidopsis et al., It will be interesting to of are involved in flavonoid gene expression in species petunia and maize. additional identified by the petunia regulatory et al., and the Arabidopsis et al., new members of the family of and have to in maize and in directly expression of a DFR gene as well as an protein, whereas is required for expression of DFR and that these may be although there is from both sequence and experimental data to that are not of and et al., 2000). of genes identified by regulatory loci such as petunia and maize and Arabidopsis as well as analysis of the in flavonoid regulatory plant species, in some of the many that in the flavonoid gene regulation The of the activity of regulatory species is another important of example, Grotewold et recently shown that the of maize and with is by a number of specific in the and an essential aspect of regulation in this are for helping the of both structural and involved in flavonoid biosynthesis and for the of plant examples have been In one at and showed that genes exhibiting altered expression in maize cell lines flavonoid pathway both maize flavonoid genes as well as sequences et al., 2000). In the second example, and his have expression of both and candidate phenylpropanoid pathway genes and as the of this et al., 2000). Together with genetic and these efforts are to understanding of flavonoid biosynthesis is controlled and this information may be used to engineer flavonoid metabolism in plant The of the and organization of flavonoid enzymes was first by more years ago, together with the that the enzymes of general and flavonoid biosynthesis were to function as multienzyme (Stafford, The that these pathways may be as enzyme that facilitate the direct or of between is for a number of example, there is for substrates at the branch these the are and and the of these compounds appears to be there is the for these pathways to to and to the amounts of end products that are The first to this largely from group University, who used cell and experiments to that and were in the with the of the for review, see This group also data from experiments an of with the of the but not with or in The results of this work to a model for phenylpropanoid and flavonoid synthesis a of of enzymes that is through with membrane that include and has now been in of a flavonoid enzyme and experiments that there are direct between and DFR in Arabidopsis and Winkel-Shirley, 1999). However, the data do not point to a of enzymes, but to a in which not the enzyme in the pathway, and also and In the of with the first described by has now also been in Arabidopsis, together with of this enzyme with the that both are enzymes and Winkel-Shirley, 2001). a in the Arabidopsis F3′H gene that most of the of this P450 enzyme results in altered of and that F3′H may function as of a membrane for other enzymes of the flavonoid pathway, as first suggested by There have also been that the isoflavonoid branch pathway as an enzyme This pathway two cytochrome P450 that function as membrane IFS and (Fig. 1). first for the of an enzyme from this pathway, isoflavone reductase, with the in cell experiments with in alfalfa together with for in and in in the for have that isoflavone O-methyltransferase is of a metabolic et al., 1998; and 2000). It is interesting that this enzyme between the two P450 IFS and I2′H, in isoflavonoid These recent together with for between and in the general phenylpropanoid pathway and and and 1999), that the organization of these may an important in understanding plant metabolism is Although the flavonoid pathway is to be an of a a enzyme it is also that this organization metabolic engineering by the of to enzymes and 1999), at the same providing for the of into or branch A great of work is in this including efforts to define protein to plant cells or a variety of to the production of specific and to in the organization of enzyme in response to and information is also the transport of flavonoids from the of synthesis in the to in the or cell of pigments to the in the maize and petunia and also in both a and a to the family of et al., 1995; et al., 1998). The enzymes, in petunia and in maize, are and are able to in of flavonoids in a variety of plant et have recently suggested that and may function as and that transport is by a with reduced to the transport of in the A is in Arabidopsis, and of the gene has that transport of proanthocyanidin into the in the seed coat involves a protein to the and family of in this species et al., 2001). Erich group has new from analysis of maize cells with a of flavonoid synthesis (Fig. 1), for the transport of yellow or compounds to the and cell respectively (for review, see 2001). These are of the subcellular that in cells and 1990). for of flavonoid enzymes in in Arabidopsis cells and Winkel-Shirley, may be to this transport between the of genes that are essential for this and the analysis of the cell of the system, elucidation of the molecular the of flavonoid compounds in of the cell may be on the This is an of central in understanding flavonoid biosynthesis is controlled and may provide additional into engineering this metabolic pathway. The elucidation of the of and from alfalfa by (The and Richard Dixon's is one of the most recent developments in understanding the flavonoid pathway in three et al., 1999; et al., In addition to providing new information the of flavonoid as of the of and the synthase et al., are providing a great of information the of plant This is for engineering these enzymes to produce new similar to has been with the bacterial It is that homology of the can be used to activities of enzymes in at some (for review, see and 1999). of the Arabidopsis enzyme has also into specific mutations reduce not by the but also by the protein or with et al., 2000). on the other has a and enzyme activity that are unique to the has the first information on the alfalfa enzyme naringenin chalcone and and catalyzes the of The also that may be important in the of enzymes in and other plant Efforts are to the of Arabidopsis flavonoid enzymes to facilitate the of experiments to define the of these in the enzyme It is that the that have been are providing information for studying a variety of of flavonoid biosynthesis, from to and subcellular The of flavonoid biosynthesis plants has long the of the pathway and structural and regulatory Biochemical data first the that this pathway been from In the of the enzymes of flavonoid biosynthesis are members of three classes of enzymes found in all the flavonol and and and cytochrome P450 F3′5′H, and 1; and 1999). and on the other appear to have a more in appears to be unique to plants in both sequence and et al., is a member of the plant synthase which also and This family of enzymes uses similar and similar or substrates to produce a wide variety of Although these enzymes are not to the bacterial or fungal other are in In recent work has a sequence with plant including the enzyme identified by in Arabidopsis, which the first step in biosynthesis et al., 1999; et al., 2000). on the gene family in point to gene and of this enzyme over the of et al., 2000). It has also been suggested that has evolved from in plant species, based on the results of and structural and the that is found in a number of plant species (for review, see 1997). for of specific enzyme activities from flavone which is as a dioxygenase in and a P450 in snapdragon 1990). In some of the of the flavonoid pathway may have evolved from the enzymes, as suggested for which may in flavonoid transport as directly these compounds to et al., 2000). It is interesting to that the genes in the flavonoid pathway appear to have evolved more the genes et al., 1999). The of genome sequence and protein information additional on the of the flavonoid pathway and also provide into such as the of in enzymes that to control at major branch The flavonoid biosynthetic pathway has been one of the most metabolic in As with new of information appears to a number of and At the same time, new are providing the opportunity to flavonoid biosynthesis, not as an of but as of a and metabolic The to now flavonoid enzymes, for the very first time, in three and to the of the pathways of metabolism using and metabolic are to much more this The of for that include Arabidopsis, the and the model are also to this metabolic model from new It is even for pathways flavonoid biosynthesis, these are The the members of and two for on the are also to Chris Cobbett, Erich Tanaka, and for information to and to Erich Ann Cathie and Francesca Quattrocchio for providing
DOI: 10.1104/pp.126.2.485